CLINICAL VIGNETTE 2017; 3:1
MANAGEMENT OF NON-FUNCTIONING PITUITARY TUMOURS
Editor-in-Chief: Olufemi E. Idowu. Neurological surgery Division, Department of Surgery, LASUCOM/LASUTH, Ikeja, Lagos, Nigeria.
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MANAGEMENT OF NON-FUNCTIONING PITUITARY TUMOURS
DR JULIUS M. VITOWANU
Department of Surgery, Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria.
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CASE PRESENTATION • NAME: M.R.
• AGE: 62 years • GENDER: Male
• OCCUPATION: Fashion designer • PC:
Bilateral visual impairment x2years
Headache x2years
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CLINICAL EVALUATION HISTORY • Difficulty with vision (loss of peripheral vision) started with the left eye, progressed to the right 6 months later • Headache was around the vertex, dull, persistent, aggravated by sneezing, coughing, and straining; wakes him at night EXAMINATION
• Conscious ,not pale ,anicteric ,acyanosed, nil pedal oedema • Pupils 3.5mm in size bilaterally, reactive to light • Right eye– no light perception, Left eye- light perception
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INVESTIGATIONS • Assessment: Sellar/suprasellar mass with optic chiasma compression • Pituitary function Test: low LH and Testosterone. – LH – 0.65µIU/ml (1.8-2.0) – testosterone <1.0ng/ml
SURGERY • Right pterional craniotomy with sellar tumor excision • Intra-operative findings ; – stretched , splayed , bowed right optic nerve – Firm haemorrhagic sellar/suprasellar tumour Copyright- Frontiers of Ikeja Surgery, 2017; 3:1
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POST-OPERATIVE • Discharged to clinic, 2 weeks after surgery • Follow up visit 2 weeks after discharge – Visual Deficit remains, headaches resolved
• Post-operative Pituitary function test – Low cortisol – 3.1µg/dl (5- 23) – Low TSH – 0.069µIU/ml (0.3 – 4.2) – Low T4 - <20µIU/ml
• Post-operative Treatment – Levothyroxine 100ug daily – Tabs hydrocotisone 10mg daily Copyright- Frontiers of Ikeja Surgery, 2017; 3:1
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PITUITARY ANATOMY Comprises anatomically and functionally distinct Anterior pituitary lobe (adenohypophysis) Posterior pituitary lobe (Neurohypophysis) Entirely ectodermal in origin Adenohypophysis Develops from Rathke’s pouch Upward invagination Neurohypophysis Develops from the infundibulum Downward extension of the floor of the diencephalon
Occupies a cavity of the sphenoid bone called sella turcica Roof is formed by diaphragm sellae The stalk of pituitary is attached above to the floor of third ventricle Measures about 15 mm in antpost and 12 mm in supero inferior axis Weighs- 0.5 gm
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NON-FUNCTIONING PITUITARY TUMOURS (NFPA) • Tumours of the pituitary gland that are characterized by the absence of clinical and biochemical evidence of pituitary hormonal overproduction • Constitute 25 – 30 % of pituitary tumours • Usually histologically benign • Symptoms are usually due to size and pressure effects on the surrounding structures – velocity and direction of tumour growth
Folate receptor α (FRα), a high-affinity folate transporter, is significantly overexpressed in clinically nonfunctional adenomas but not in functional adenomas
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AETIOPATHOGENESIS • Monoclonal in origin ,due to genetic mutations in a single cell • Precise mechanisms yet to be understood Oncogenes • c-myc oncogene • stimulatory guanine nucleotide-binding protein (gsp) gene • pituitary tumor transforming gene (PTTG • Cyclin D1 (CCND1) • H-ras oncogene) Copyright- Frontiers of Ikeja Surgery, 2017; 3:1
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CLINICAL PRESENTATION • Asymptomatic- Incidentalomas are mostly microadenomas (about 2/3), confined to the sella turcica and usually do not cause any signs or symptoms • Symptomatic-Due to pressure effect of enlarging pituitary mass in the cranial cavity – Headaches – Vomiting – Visual defect: Bitemporal field defects are the most common, Impaired visual acuity, abnormal pupillary light reaction, color vision can be affected, ophthalmoplegia, diplopia, ptosis – Hypopituitarism - from mass compression of normal gland, or secretion of inactive hormonal subunits – Galactorrhea – pituitary stalk effect – Pituitary apoplexy- due to acute hemorrhage or infarction of a pituitary gland, Can be lethal
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DIFFERENTIAL DIAGNOSIS • • • • • • • • •
Craniopharyngiomas Meningiomas Neurofibromas Ectopic germinomas Metastatic tumors. Sarcoid Tuberculomas Carotid artery aneurysm Sphenoid sinus mucocele Copyright- Frontiers of Ikeja Surgery, 2017; 3:1
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NEUROIMAGING • MRI – Gold standard – Intrasellar mass – isointense on T1 –weighted , different enhancement patterns post contrast • • • •
Size Degenerative changes Extra sella extension Consistency
• CT scan – Provides details of bone anatomy – diagnostic imaging study of choice in patients who are unable to undergo an MR study. – Useful in preoperative planning • for the definition of the best route from the nasal cavity toward the sellar
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EVALUATION • Imaging – Identify the lesion – Define spatial situation of the lesion (presurgical planning) – Verify removal of the lesion (postsurgical follow-up)
• Assessment of pituitary function • Ophthalmological assessment – visual field perimetry; visual field defect – Visual Evoke Potential ; latency delay , amplitude reduction
• Histopathological analysis of surgical specimen – Confirm diagnosis – Immunohistochemistry- primary hormones, Ki-67, P53
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TREATMENT
Non-operative- watchful waiting Surgery Radiotherapy Medical therapy
SURGERY General indication • Pituitary apoplexy • Progressive mass effect - Visual deficits or cranial nerve palsy. Goals • Normalization of excess of hormone secretion, if any • Preservation or even restoration of normal pituitary function • Elimination of mass effect • Preservation or restoration of visual acuity and/or visual field • Prevention of tumor recurrence • Achievement of a complete pathologic diagnosis Copyright- Frontiers of Ikeja Surgery, 2017; 3:1
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SURGERY Surgical Approaches for Pituitary Tumors 1. Trans-Sphenoidal Approach • Microscopic – Sublabial – Trans-septal – Endonasal
• Endoscopic • Combined or endoscope-assisted microsurgery 2. Transcranial Approach • Pterional or frontolateral • Subfrontal unilateral • Subfrontal bilateral interhemispheric • Supraorbital craniotomy • Radical combine approach – recurrence
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SURGERY Indications for transcranial approach • Doubt about diagnosis • Failed transphenoidal surgery – Intrinsic tumour characteristics – Failure of suprasella extension to descend – Falure to remove adequate amount of tumour
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Para/extrasella extension Coexistence aneurysms Ectactic carotid artery Severe sinus infection
Complications • • • •
• • • • •
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Frontal lobe damage Frontal lobe cyst Anosmia Perioperative optic nerve damage Vascular injuries Hypothalamic damage CSF leakage Electrolyte abnormalities Post op visual deterioration
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RADIOTHERAPY • Mainly used as complementary to surgery – tumors not completely resected by surgery – for patients who, at diagnosis, already present aggressive tumors – tumors with pathologic characteristics that demonstrate aggressiveness
• Primary therapy – patients with tumors proximate or reaching the optic pathway and concurrently present high surgical risk or surgery refusal
• Conventional – in fractionated doses four to five times a week for four weeks
• Stereotactic – Fractionated – Radiosurgery • Gamma knife • Cyber knife
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MEDICAL TREATMENT • Well tolerated and safe molecules, able to reduce tumour size in some instances • Somatostatin analogues • Dopamin agonists – particularly tumours that express long isoforms of D2 receptor • The expression of D2 short rather than D2 long isoform was found to be associated with the most favourable response of the tumor to cabergoline treatment Pivonello et al. • Other drugs – Temozolomide
WATCHFUL WAITING • Employed in carefully selected patients • Regular assessment of pituitary function, MRI and visual field is required.
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FOLLOW UP • Imaging – Imaging exam of the sellar region, preferably MRI, at least 3 months after surgery – Annual MRI in the first 5 years – Every 2-3 years thereafter
• Pituitary function test – Evaluation of pituitary function 1-3 months after the procedure – Then every 6-12 months
• Ophthalmological assessment – Evaluation of the visual field through visual perimetry one month after surgery – Then Annual visual field perimetry
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REFERENCES • • • • •
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John A. Jane Jr. et al. Pituitary tumours. Functioning and Nonfunctioning. Youmans neurological surgery 16th edition ch 34 pp 1476 -1509 Pablo S Recinos ,C Rorry Goodwin et al ;SCHMIDEK & SWEET OPERATIVE NEUROSURGICAL TECHNIQUES: transcranial surgery for pituitary macroadenomas Ch 23 pp 280- 91 Maria Licia, Calado de Aguiar, Ribeiro Cury; Non-functioning pituitary adenomas: clinical feature, laboratorial and imaging assessment, therapeutic management and outcome. Clin Endocrinol. Mônica R. Gadelha. Rua Prof. Rodolpho Paulo Rocco,Arch Endocrinol Metab. 2016;60(4):374-90 Soto-Ares G, Cortet-Rudelli C, Assaker R, Boulinguez A, Dubest C, Dewailly D, et al. MRI protocol technique in the optimal therapeutic strategy of non-functioning pituitary adenomas. Eur J Endocrinol. 2002;146(2):179-86 Park P, Chandler WF, Barkan AL, Orrego JJ, Cowan JA, Griffith KA, et al. The role of radiation therapy after surgical resection of nonfunctional pituitary macroadenomas. Neurosurgery. 2004;55(1):100-6; discussion 67. C. A. Jaffe, “Clinically non-functioning pituitary adenoma,” Pituitary, vol. 9, no. 4, pp. 317–321, 2006. View at Publisher Pivonello R, Matrone C, Filippella M, Cavallo LM, Di Somma C, Cappabianca P, Colao A, Annunziato L & Lombardi G. Dopamine receptor expression and function in clinically non-functioning pituitary tumors: comparison with the effectiveness of cabergoline treatment. Journal of Clinical Endocrinology and Metabolism 2004 89 1674–1683
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